Detection of trace chemicals in solid and liquid samples may be achieved by methods that combine chromatography techniques with mass spectrometry. While sensitive, such methods are labor intensive, time consuming, and costly. They also require expensive and bulky equipment, and hence are not portable.
Surface enhanced Raman Spectroscopy (SERS) offers an attractive alternative for chemical analysis. SERS is a powerful technique for chemical and biomolecular identification. Typically, a SERS analysis involves spotting a μL-volume of sample onto a nanofabricated SERS substrate, allowing it to dry, and then detecting the Raman scattering. Due to the optical and chemical enhancement of nanostructures, single molecule identification has been demonstrated with SERS.
Unfortunately, the high cost and complications associated with the fabrication of conventional SERS-active substrates have prevented the wide use of SERS. Furthermore, these substrates exhibit limited shelf life, with progressive reduction in SERS activity due to oxidation of the nanostructures (see Erol M. et al. (2009), “SERS Not To Be Taken for Granted in the Presence of Oxygen,” J. Am. Chem. Soc. 131:7480-1).
To make SERS more applicable, attempts have been made to combine microfluidic techniques with SERS (see Huh Y. S. et al. (2009), supra, Microfluid. Nanofluid. 6:285-297; Lim C. et al. (2010) “Optofluidic platforms based on surface-enhanced Raman scattering,” J. Analyst 135:837-844; Yin Y. et al. (2011) J. Mater. Res. 26:170-185; Huh Y. S. et al. (2009) “Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells,” Lab Chip 9:433-439; Measor P. et al. (2007) Appl. Phys. Lett. 90:211107; Yang X. et al. (2010) J. Opt. Soc. Am. A. 27:977; Choi I. et al. (2011) “Size-selective concentration and label-free characterization of protein aggregates using a Raman active nanofluidic device,” Lab Chip. 11:632-8; Cho H. et al. (2009) “Label-free and highly sensitive biomolecular detection using SERS and electrokinetic preconcentration,” Lab Chip 9:3360-3363; Han B. et al. (2011) “Application of silver-coated magnetic microspheres to a SERS-based optofluidic sensor,” J. of Phys. Chem. C 115:6290-6296; Park S-M et al. (2009) “A method for nanofluidic device prototyping using elastomeric collapse,” Proc. Natl. Acad. Sci. 106:15549-15554). However, such microfluidic SERS devices introduce additional complexity to their fabrication, and may decrease sensitivity due to difficulties in the optical coupling, decreased sample volume, and the inability to concentrate the analyte by drying.
Various attempts have been made to translate the capabilities of SERS to a practical microsystem that can be utilized for routine analysis of samples in the lab or in the field (Liu G. L. and Lee L. P. (2005) Appl. Phys. Lett. 87:074101; Measor P. et al. (2007), supra, Appl. Phys. Lett. 90:211107; Strehle K. R. et al. (2007) “A Reproducible Surface-Enhanced Raman Spectroscopy Approach. Online SERS Measurements in a Segmented Microfluidic System,” J. Anal. Chem. 79:1542-1547; White I. M. et al. (2007) “SERS-based detection in an optofluidic ring resonator platform,” Optics Express 15(25):17433-17442; Quang L. X. et al. (2008) “A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis,” Lab Chip 8:2214-2219; Choi D. et al. (2009) “Additional amplifications of SERS via an optofluidic CD-based platform,” Lab Chip 9:239-243; Gamby J. et al. (2009) “Polycarbonate microchannel network with carpet of Gold NanoWires as SERS-active device,” Lab Chip 9:1806-1808; Huh Y. S. et al. (2009), supra, Lab Chip 9:433-439; Wang G. et al. (2009) “Surface-enhanced Raman scattering in nanoliter droplets: towards high-sensitivity detection of mercury (II) ions,” J. Anal. Bioanal. Chem. 394:1827-1832; Wang M. et al. (2009) 6:411-417; Lim C. et al. (2010), supra, J. Analyst 135:837-844). In general, such SERS systems require microfabrication, and in some cases require nanofabrication to produce a surface with a metal nanostructure. As a result, chemical and biomolecular detection using SERS has been costly on a per-sample basis. Furthermore, SERS-active substrates produced through such conventional techniques have a short shelf life and must be used quickly. SERS activity of silver nanostructures has been shown to decrease drastically as a result of oxidation within a week (e.g., see Erol et al (2009), supra, J. Am. Chem. Soc. 131:7480-7481; Qi H. et al. (2010) “The effect of size and size distribution on the oxidation kinetics and plasmonics of nanoscale Ag particles,” Nanotechnology 21:215706). Thus, such conventional SERS systems have not been found practical for routine laboratory analysis of chemicals and biomolecules, and are not an option for field-based applications. Conventional SERS methodologies are therefore limited to laboratory settings due to their high cost and short shelf life.
Thus, there is a need for a relatively simple and low-cost SERS analytical system which overcomes some or all of the above-noted problems.